Gen protects against Alzheimer's

Research: Gene mutation prevents Alzheimer's

07/12/2012

Icelandic researchers have discovered a gene mutation that significantly reduces the risk of Alzheimer's disease. Due to the special gene variant, the protein deposits in the brain, which are considered to trigger the disease, prevented. Also, the usual age-related limitations of cognitive performance were significantly lower in individuals with the particular gene mutation.

While numerous genes have been discovered in recent decades that are considered to be a risk factor for Alzheimer's, so far not a gene variant has been known that has a protective effect against the neurodegenerative disease. However, the gene mutation now discovered by the Icelandic researchers apparently shows exactly this effect. The gene variant changes the structure of the so-called Alzheimer's precursor protein (APP), so that less disease-causing protein deposits (formed by beta-amyloids) arise in the brain, reports the research team to Kari Stefansson from the University of Iceland in Reykjavik in the journal „Nature“. Among other things, the Icelandic researchers were supported by scientists from the University of Oslo, the Karolinska Institute in Stockholm and the Institute of Human Genetics at the University of Tübingen.

Heredity of 1,800 Icelanders investigated
Scientists studied the genetic makeup of 1,795 Icelanders aged over 80 years. In the subjects who showed no signs of dementia, the researchers discovered a gene variant that apparently protects against dementia and Alzheimer's. Kari Stefansson, who also works for the gene research company „deCODE genetics“ working in Reykjavik, with his international team, had studied the individual differences in the DNA sequence of the gene responsible for the formation of the Alzheimer's precursor protein. The gene provides the blueprint for the APP, which is then decomposed by the two enzymes gamma and beta-secretase, which also produces beta-amyloid. This, in turn, causes the nerve cells to die and form insoluble deposits in the brain tissue, resulting in diminished cognitive performance and eventually Alzheimer's disease. In the DNA analysis, the researchers discovered a special gene mutation that causes a structural change in the Alzheimer's precursor protein, which allows the enzyme beta-secretase to cleave the APP worse. As a result, 40 percent fewer harmful beta-amyloids are produced and the risk of Alzheimer's disease is significantly reduced, the researchers said.

Gene mutation protects against Alzheimer's disease and age-related degradation of brain function
Some of the non-demented 80 to 100-year-old study participants are saved from Alzheimer's disease by the mutation of the APP gene, report Kari Stefansson and colleagues. Their overall mental power was also well above average thanks to the gene mutation, the Icelandic researchers continue. In memory tests, the sane people carrying the mutant gene performed much better than non-demented subjects of the same age without the corresponding gene variant. Thus, the gene mutation not only protects against Alzheimer's, but apparently also slows the natural decline in cognitive performance in old age, the experts explained. Since the effect is due to an impairment of the APP cleavage by the enzyme beta-secretase, the current research results are also a confirmation of the relatively new strategy of Alzheimer treatment or prevention by drugs for the inhibition of beta-secretase, Stefansson and colleagues report , Possibly, the pharmacological beta-secretase inhibition, for which the first active substances are already available, may also generally stabilize mental performance in old age, according to the Icelandic researchers.

According to Kari Stefansson support the current „Results indirectly hypothesize that Alzheimer's disease and the normal decline in cognitive brain performance in the elderly may be based on the same mechanisms.“ In that „Nature“-items „A mutation in the APP protects against Alzheimer's disease and age-related cognitive decline“ the researchers come to the conclusion that „Alzheimer's dementia could be the extreme form of age-related cognitive decline ".

Advances in dementia research required
How important advances in dementia research and therapy are is illustrated by the numbers of diseases presented by the researchers. According to Kari Stefansson and colleagues, more than five percent of the population over the age of 60 suffer from dementia in western industrialized countries. Two-thirds of those affected have Alzheimer's. With increasing age, the probability of a disease increases continuously, so that at least a quarter of the 90-year-olds suffer from Alzheimer's dementia, the scientists report. There is still no prospect of a cure, and the progression of the disease can not be stopped yet. The only chance on the basis of the existing treatment methods is a delay in the course of the disease, so that if diagnosed early, one to two years can be gained in which the patients stay fit for longer. (Fp)

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Image: Martin Gapa